This invention relates to semi-synthetic cephalosporin antibiotics. In particular, it relates to cephalosporin compounds wherein the cephalosporin bicyclic nucleus is substituted in the 3'-position by an oxime-substituted pyridinium, quinolinium, or isoquinolinium group and in the 7-position with a 2-(amino-substituted heterocyclic)-2-oximinoacetamido group.
Cephalosporin antibiotic compounds substituted in the 3'-position with a quaternary ammonium group have been known for some time. One of the first derivatives of cephalosporin C which was prepared was cephalosporin C.sub.A (pyridine), Hale, Newton, and Abraham, Biochem. J., 79 403 (1961). Cephaloridine, the wellknown clinical antibiotic, is the 3'-pyridinium cephalosporin, 7-(.alpha.-thienylacetamido)-3-(pyridinium-1-ylmethyl)-3-cephem-4-carboxyl ate.
Recent research has again centered on the synthesis and study of 3'-quaternary ammonium derivatives of cephalosporins. Recently, Heymes et al., U.S. Pat. No. 4,152,432, described semi-synthetic cephalosporin antibiotics wherein the 7-position side chain is a 7-[2-(2-aminothiazol-4-yl)-2-alkoxyiminoacetamido] group. 3'-Quaternary ammonium derivatives of the cephalosporins having this side chain have been described recently by Belgium Pat. No. 853,545, and more recently by O'Callaghan, et. al., in U.S. Pat. No. 4,258,041. The latter-described compounds have a carboxy-substituted branched alkyl group on the oxygen of the oxime function in the 7-position side chain.
Continual improvement is sought in antibiotic therapy to overcome deficiencies in the existing practice. The semi-synthetic cephalosporin antibiotics have long been recognized as broad spectrum antibiotics, and several have achieved clinical importance. Continued research with the cephalosporin antibiotics has, as one of its goals, the development of antibiotics having higher activity against resistant microorganisms, particularly the gram-negative microorganisms, as well as antibiotics with an even broader spectrum of activity.